RESUMO
SIGNIFICANCE: There is a clinical necessity for dry eye disease treatments that perform across a broad range of presenting patient severities. Varenicline solution nasal spray (VNS), a unique cholinergic agonist ocular surface-sparing nasal spray therapy, demonstrated significant improvement in both signs and symptoms of dry eye disease in subjects with mild, moderate, and severe symptoms as the clinical studies enrolled a more real-world patient population. PURPOSE: This study evaluated efficacy outcomes for VNS in patients with mild-moderate and severe dry eye disease. METHODS: An analysis of integrated data from two randomized clinical trials, ONSET-1 (NCT03636061) and ONSET-2 (NCT04036292) (vehicle control [VC], n = 294; VNS 0.03 mg, n = 308), was performed. Adults 22 years or older with dry eye disease, Ocular Surface Disease Index score of ≥23, corneal fluorescein staining score of ≥2 in ≥1 regions/≥4 all regions, and Schirmer Test Score (STS) of ≤10 mm (no restrictions on Eye Dryness Score [EDS]) were included in this study. Efficacy was evaluated using analysis of covariance among pre-specified subgroups of mild-moderate and severe baseline disease severity defined by STS (≤5 vs. >5) and EDS (<60 vs. ≥60). Consistency of effect was evaluated by interaction tests. RESULTS: No treatment-subgroup interactions were observed for all end points ( P > .05). The odds of achieving a ≥10-mm improvement in STS for VNS versus VC for patients with baseline STS ≤5 and >5 were 3.4(95% confidence interval, 2.0 to 5.6) and 2.3(1.3 to 4.0) and for EDS of <60 and ≥60 were 3.4(1.9 to 6.1) and 2.5(1.5 to 4.0). Least-squares mean treatment/VC differences in change from baseline in EDS for patients with baseline STS ≤5 or >5 were -7.4(95% confidence interval, -12.5 to -2.4) and -2.8(-8.7 to 3.1); EDS of <60 and ≥60 were -2.9(-8.3 to 2.5) and -8.1(-13.6 to -2.6). CONCLUSIONS: Compared with VC, VNS improved tear production and patient-reported symptoms in patients with dry eye disease, demonstrating consistency of effect regardless of initial presenting severity.
Assuntos
Síndromes do Olho Seco , Sprays Nasais , Adulto , Humanos , Síndromes do Olho Seco/tratamento farmacológico , Soluções Oftálmicas , Gravidade do Paciente , Lágrimas , Resultado do Tratamento , Vareniclina/uso terapêuticoRESUMO
Excised redundant, forniceal "conjunctival" tissue from a 67-year-old man who experienced a chemical injury to his OS 25 years earlier was evaluated histopathologically with the hematoxylin-eosin, periodic acid Schiff (PAS) with and without diastase, mucicarmine, and Alcian blue methods. Additional immunoperoxidase testing for gross cystic disease fluid protein-15 (GCDFP-15) was undertaken. Non-keratinizing squamous epithelium composed of 8 to 10 layers of swollen keratinocytes without goblet cells surmounted a variably dense and well-vascularized collagenized lamina propria deep to which, in submucosal fibroadipose tissue, was embedded an accessory gland. The acini of the gland were composed of both GCDFP-15-positive serous cells and mucicarmine-positive goblet cells, indicating they were seromucinous rather than entirely serous, as is characteristic of normal lacrimal glandular tissue. Different features of the surface epithelium, the lamina propria, and the submucosa can separate the conjunctival and oral mucous membranes. A close analysis of the cytologic composition of associated accessory glands can reinforce the correct diagnosis of an oral mucous membrane graft when the past surgical history is unclear, because only serous cells but not mucocytes comprise the lacrimal glandular units.
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Queimaduras Químicas/cirurgia , Túnica Conjuntiva/patologia , Ectrópio/patologia , Queimaduras Oculares/cirurgia , Mucosa Bucal/patologia , Mucosa Bucal/transplante , Procedimentos Cirúrgicos Oftalmológicos/métodos , Idoso , Queimaduras Químicas/complicações , Túnica Conjuntiva/lesões , Túnica Conjuntiva/cirurgia , Ectrópio/etiologia , Ectrópio/cirurgia , Queimaduras Oculares/complicações , Humanos , Masculino , Procedimentos de Cirurgia Plástica/métodosRESUMO
Cataracts are a leading cause of preventable blindness globally. Although care varies between developing and industrialized countries, surgery is the single effective approach to treating cataracts. From the earliest documented primitive cataract removals to today's advanced techniques, cataract surgery has evolved dramatically. As surgical techniques have developed, so have approaches to surgical pain management. With current cataract surgical procedures and advanced technology, anesthesia and intraoperative pain management have shifted to topical/intracameral anesthetics, with or without low-dose systemic analgesia and anxiolysis. Despite this, pain and discomfort persist in some patients and are underappreciated in modern cataract surgery. Although pain management has progressed, opioids remain a mainstay intraoperatively and, to a lesser extent, postoperatively. This article discusses the evolution of pain management in cataract surgery, particularly the use of opioids and the associated risks as well as how ophthalmology can have a positive impact on the opioid crisis.
Assuntos
Catarata , Oftalmologia , Analgésicos Opioides/uso terapêutico , Anestesia Local/métodos , Anestésicos Locais/uso terapêutico , Catarata/complicações , Humanos , Dor , Manejo da Dor/efeitos adversos , Dor Pós-Operatória/tratamento farmacológicoRESUMO
Background: Iontophoresis is a noninvasive delivery system designed to overcome barriers to ocular penetration of topical ophthalmic medications by employing a low-amplitude electrical current to promote the migration of a charged drug substance across biological membranes. Trans-scleral iontophoresis of dexamethasone phosphate has demonstrated dramatically increased intraocular concentrations of dexamethasone in rabbit ocular tissues compared with topical instillation, including 50- to 100-fold greater aqueous humor concentrations. Methods: This article reviews available data on recent clinical applications of iontophoretic ophthalmic drug delivery. Results: The EyeGate II delivery system (EGDS) is a trans-scleral iontophoresis system that has been used in conjunction with EGP-437, a proprietary-charged formulation of dexamethasone phosphate for iontophoretic delivery. In patients with noninfectious anterior uveitis, EGP-437, delivered through 2 iontophoretic treatments using the EGDS, demonstrated similar efficacy to topical prednisolone acetate 1% eye drops instilled 8 times daily over 28 days, suggesting the potential to decrease or eliminate the need for daily dosing of topical steroids in this patient population. Other applications for EGP-437 delivered through the EGDS that have been explored in clinical trials include treatment of dry eye, postsurgical inflammation and pain, and scleritis. In addition, transcorneal iontophoresis has been used outside of the United States to enhance riboflavin penetration in patients undergoing corneal cross-linking as therapy for progressive keratoconus. Conclusions: The reviewed studies demonstrate the feasibility of using iontophoresis to enhance drug delivery to ocular tissues and support the potential of this noninvasive technique across a range of ophthalmic indications.
Assuntos
Sistemas de Liberação de Medicamentos , Síndromes do Olho Seco/tratamento farmacológico , Inflamação/tratamento farmacológico , Soluções Oftálmicas/uso terapêutico , Dor/tratamento farmacológico , Uveíte Anterior/tratamento farmacológico , Animais , Humanos , Iontoforese , Soluções Oftálmicas/administração & dosagemRESUMO
Purpose: Corneal collagen crosslinking (CXL) through an intact epithelium (epi-on) at high irradiance could potentially improve patient comfort, visual recovery, and clinical workflow compared to conventional epi-off CXL. However, intact epithelium limits stromal delivery of the oxygen, photosensitizer, and ultraviolet-A (UV-A) radiation needed to drive CXL. This ex vivo study evaluated three different epi-on CXL protocols compared to positive and negative controls, specifically focusing on the impact of supplemental oxygen. Endpoints included stromal oxygen levels, stiffness of crosslinked tissue, and acute flattening of whole eyes.Materials & Methods: Ex vivo porcine eyes were held in a custom environmental chamber. Intrastromal oxygen levels were continuously measured before, during, and after UV illumination by a fiberoptic probe inserted into a laser-cut flap. Accelerated, high irradiance, epi-on CXL protocols using riboflavin formulated with benzalkonium chloride (BAC) were studied, with and without supplemental oxygen. These were compared to an alternate, low irradiance, epi-on protocol using riboflavin formulated with sodium iodide. Both negative (no CXL) and positive (epi-off modified Dresden protocol) controls were performed. Post-CXL elastic modulus was measured using extensiometry and anterior tangential curvature was measured using a Scheimpflug tomographer.Results: Protocols including supplemental oxygen resulted in an approximately 5-fold increase in stromal oxygen levels prior to CXL. During epi-on, high-irradiance UV-A delivery under hyperoxic conditions, an aerobic state was maintained. Conversely, under normoxic conditions, stromal oxygen rapidly depleted to 0-5% for all other protocols. The combination of supplemental oxygen, BAC formulation, and high-irradiance UV-A resulted in the largest biomechanical changes and most pronounced flattening effects of the three epi-on protocols.Conclusions: Ex vivo analysis of stromal oxygen levels, corneal stiffness, and acute anterior curvature change indicates that simultaneous optimization of the oxygen environment, riboflavin formulation, and UV-A protocol can significantly increase the effects of corneal collagen crosslinking.
Assuntos
Colágeno/farmacologia , Substância Própria/metabolismo , Reagentes de Ligações Cruzadas/farmacologia , Ceratocone/metabolismo , Oxigênio/metabolismo , Fotoquimioterapia/métodos , Riboflavina/farmacologia , Animais , Substância Própria/diagnóstico por imagem , Topografia da Córnea , Modelos Animais de Doenças , Ceratocone/diagnóstico , Ceratocone/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Suínos , Raios UltravioletaRESUMO
PURPOSE: To evaluate the safety and efficacy of dexamethasone phosphate ophthalmic solution (EGP-437) delivered by a transscleral iontophoresis delivery system (EyeGate II) compared to that of topical prednisolone acetate 1% (PA 1%) in subjects with noninfectious anterior uveitis. DESIGN: Prospective, randomized, double-masked, parallel group, noninferiority clinical trial. METHODS: A total of 193 subjects with active noninfectious anterior uveitis (anterior chamber [AC] cell count ≥11 cells) were randomized to EGP-437 delivered by iontophoresis (days 0 and 7) or self-administered PA 1% daily (tapered schedule, days 0-28). Masking was maintained with placebo iontophoresis or eye drops. The primary efficacy endpoint was the proportion of subjects with an AC cell count of zero on day 14. Noninferiority of EGP-437 was defined if the lower limit of the confidence interval (CI) for the difference (EGP-437 minus PA 1%) was less than -10%. RESULTS: At day 14, 32 of 96 EGP-437 subjects (33.3%) and 32 of 97 PA 1% subjects (33.0%) had an AC cell count of zero (difference, 0.34; 95% CI, -12.94 to 13.63; P = 0.064). Efficacy trended better with EGP-437 among patients with more severe baseline uveitis (AC cell count >25). Safety and tolerability were good with both treatments. EGP-437 subjects experienced fewer IOP elevations ≥6 mm Hg versus PA 1% subjects (13 vs 24 incidents, respectively, through day 28). CONCLUSIONS: Despite clinically similar response rates, statistical noninferiority of EGP-437 versus a tapered regimen of PA 1% was not achieved. Numerical trends suggesting fewer IOP elevations with EGP-437, similar efficacy overall, and possibly better efficacy in more severe disease warrant further study.
Assuntos
Dexametasona/análogos & derivados , Sistemas de Liberação de Medicamentos , Glucocorticoides/administração & dosagem , Iontoforese/métodos , Prednisolona/análogos & derivados , Uveíte Anterior/tratamento farmacológico , Administração Oftálmica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Câmara Anterior/patologia , Contagem de Células , Criança , Dexametasona/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Pressão Intraocular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Prednisolona/administração & dosagem , Estudos Prospectivos , Resultado do Tratamento , Uveíte Anterior/diagnóstico , Uveíte Anterior/fisiopatologiaRESUMO
PURPOSE: To evaluate the efficacy and safety of a topical ophthalmic suspension combination of povidone-iodine 0.6% (PVP-I) and dexamethasone 0.1% (DEX) for infectious and inflammatory components of bacterial conjunctivitis. DESIGN: Randomized, double-masked, multicenter, phase 3 clinical trial. METHODS: Subjects of all ages (those <3 months had to be full-term) with a diagnosis of bacterial conjunctivitis were randomized 3:1:3 to either PVP-I/DEX, PVP-I alone, or placebo. The primary endpoint was clinical resolution in the study eye, and the key secondary efficacy endpoint was bacterial eradication, both at the day 5 visit. Adverse events (AEs) were documented at all visits. RESULTS: Overall, 753 subjects were randomized (intent-to-treat [ITT] population; PVP-I/DEX [n = 324]; PVP-I [n = 108]; placebo [n = 321]); mean and standard deviation (SD) age was 44.3 (22.9) years, and most were female (61.2%) and white (78.1%). In all treatment groups, mean treatment compliance was >98%. The modified ITT population for the efficacy analysis comprised 526 subjects. In the study eye at the day 5 visit, clinical resolution was achieved by 50.5% (111/220) subjects in the PVP-I/DEX group vs 42.8% (95/222) in the placebo group (P = .127), and bacterial eradication was achieved by 43.3% (94/217) and 46.8% (102/218), respectively (P = .500). Treatment-emergent AEs were experienced by 32.8% (106/323), 39.8% (43/108), and 19.0% (61/321) of subjects in the safety population treated with PVP-I/DEX, PVP-I, and placebo, respectively (most mild in severity). CONCLUSION: In this study, PVP-I/DEX did not demonstrate additional benefit in clinical efficacy compared with placebo in subjects with bacterial conjunctivitis.
Assuntos
Antibacterianos/uso terapêutico , Anti-Infecciosos Locais/uso terapêutico , Conjuntivite Bacteriana/tratamento farmacológico , Dexametasona/uso terapêutico , Infecções Oculares Bacterianas/tratamento farmacológico , Glucocorticoides/uso terapêutico , Povidona-Iodo/uso terapêutico , Doença Aguda , Administração Oftálmica , Adulto , Bactérias/isolamento & purificação , Conjuntivite Bacteriana/microbiologia , Conjuntivite Bacteriana/fisiopatologia , Método Duplo-Cego , Quimioterapia Combinada , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Estudos Prospectivos , Resultado do TratamentoRESUMO
PURPOSE: To evaluate netarsudil 0.02% ophthalmic solution in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). DESIGN: Double-masked, randomized, multicenter, parallel-group, noninferiority clinical study. METHODS: After a washout of all prestudy ocular hypotensive medications, 756 eligible patients with elevated IOP were randomized to receive netarsudil 0.02% once a day (q.d.) (251); netarsudil 0.02% twice a day (b.i.d.) (254); or timolol 0.5% b.i.d. (251) for 12 months, as well as a noninterventional Corneal Observation Study (COS) for patients manifesting cornea verticillata. RESULTS: On treatment, mean IOP at 8:00 AM decreased from a baseline IOP of 22.5-22.6 mm Hg to 17.9-18.8 mm Hg, 17.2-18.0 mm Hg, and 17.5-17.9 mm Hg for netarsudil q.d., netarsudil b.i.d., and timolol, respectively, over 12 months. The most frequently reported adverse events (AEs) were ocular, with the most frequent ocular AE being conjunctival hyperemia, with an incidence of 61%, 66%, and 14%, respectively. The next most frequent AEs were corneal deposits (corneal verticillata), with an incidence of 26%, 25%, and 1%, respectively, and conjunctival hemorrhage (typically petechial), with an incidence of 20%, 19%, and 1%, respectively. All 3 AEs were generally scored as mild, with conjunctival hyperemia and/or hemorrhage appearing sporadically during the study. In the observational follow-up component of this study, there was no clinically meaningful impact of corneal verticillata on visual function in affected patients. CONCLUSIONS: In this randomized, double-masked trial, once-daily dosing of netarsudil 0.02% was effective, consistently lowering IOP through 12 months, and was tolerated by the majority of patients.
Assuntos
Anti-Hipertensivos/uso terapêutico , Benzoatos/uso terapêutico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Pressão Intraocular/efeitos dos fármacos , beta-Alanina/análogos & derivados , Quinases Associadas a rho/antagonistas & inibidores , Administração Oftálmica , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Benzoatos/administração & dosagem , Benzoatos/efeitos adversos , Método Duplo-Cego , Feminino , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/fisiopatologia , Soluções Oftálmicas , Timolol/administração & dosagem , Timolol/uso terapêutico , Resultado do Tratamento , beta-Alanina/administração & dosagem , beta-Alanina/efeitos adversos , beta-Alanina/uso terapêuticoRESUMO
Importance: Determining factors associated with endothelial cell loss after Descemet stripping automated endothelial keratoplasty (DSAEK) could improve long-term graft survival. Objective: To evaluate the associations of donor, recipient, and operative factors with endothelial cell density (ECD) 3 years after DSAEK in the Cornea Preservation Time Study. Design, Setting, and Participants: This cohort study was a secondary analysis of data collected in a multicenter, double-masked, randomized clinical trial. Forty US clinical sites with 70 surgeons participated, with donor corneas provided by 23 US eye banks. Individuals undergoing DSAEK for Fuchs dystrophy or pseudophakic/aphakic corneal edema were included. Interventions: The DSAEK procedure, with random assignment of a donor cornea with a preservation time of 0 to 7 days or 8 to 14 days. Main Outcomes and Measures: Endothelial cell density at 3 years as determined by a reading center from eye bank and clinical specular or confocal central endothelial images. Results: The study included 1090 participants (median age, 70 years) with 1330 affected eyes (240 bilateral cases [22.0%]), who underwent DSAEK for Fuchs dystrophy (1255 eyes [94.4%]) or pseudophakic/aphakic corneal edema (PACE) (75 eyes [5.6%]). Of these, 801 eyes (60.2%) belonged to women and 1207 (90.8%) to white individuals. A total of 749 participants (913 eyes; 164 [21.9%] bilateral cases) had functioning grafts with acceptable endothelial images preoperatively and at 3 years postoperatively and were included in this analysis. Factors associated with a lower ECD at 3 years (estimated effect with 99% CI) in the final multivariable model included donors with diabetes (-103 [-196 to -9] cells/mm2), lower screening ECD (-234 [-331 to -137] per 500 cells/mm2), recipient diagnosis of PACE (-257 [-483 to -31] in cells/mm2), and operative complications (-324 [-516 to -133] in cells/mm2). Endothelial cell loss (ECL) from a preoperative measurement to a 3-year postoperative measurement was 47% (99% CI, 42%-52%) for participants receiving tissue from donors with diabetes vs 43% (99% CI, 39%-48%) without diabetes; it was 53% (99% CI, 44%-62%) for participants diagnosed with PACE vs 44% (99% CI, 39%-49%) for those diagnosed with Fuchs dystrophy, and 55% (99% CI, 48%-63%) in participants who experienced operative complications vs 44% (99% CI, 39%-48%) in those who did not. No other donor, recipient, or operative factors were significantly associated with 3-year ECD. Conclusions and Relevance: Donor diabetes, lower screening ECD, a PACE diagnosis in the recipient, and operative complications were associated with lower ECD at 3 years after DSAEK surgery and may be associated with long-term graft success. While causation cannot be inferred, further studies on the association of donor diabetes and PACE in recipients with lower 3-year ECD warrant further study.
Assuntos
Córnea , Perda de Células Endoteliais da Córnea/diagnóstico , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Preservação de Órgãos/métodos , Doadores de Tecidos , Transplantados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células , Criança , Edema da Córnea/cirurgia , Método Duplo-Cego , Endotélio Corneano/patologia , Feminino , Distrofia Endotelial de Fuchs/cirurgia , Sobrevivência de Enxerto/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Estudos de Tempo e MovimentoRESUMO
Vernal conjunctivitis is a bilateral, seasonal, external ocular inflammatory disease of unknown cause. Afflicted patients experience intense itching, tearing, photophobia, and mucous discharge, and usually demonstrate large cobblestone papillae on their superior tarsal conjunctiva and limbal conjunctiva. It primarily affects children, may be related to atopy, and has environmental and racial predilections. Although usually self-limited, vernal conjunctivitis can result in potentially blinding corneal complications. Treatment of chronic forms of ocular allergies may necessitate collaborative efforts between the ophthalmologist and the allergist or immunologist.
Assuntos
Conjuntivite Alérgica , Conjuntivite Alérgica/diagnóstico , Conjuntivite Alérgica/fisiopatologia , Conjuntivite Alérgica/terapia , Humanos , Comunicação Interdisciplinar , Relações InterprofissionaisRESUMO
PURPOSE: Ocular Tracking Resistance in U.S. Today (TRUST) annually evaluates in vitro antimicrobial susceptibility of Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae to ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, penicillin, azithromycin, tobramycin, trimethoprim, and polymyxin B in national samples of ocular isolates. DESIGN: Laboratory investigation. METHODS: Prospectively collected ocular isolates (197 S. aureus, 49 S. pneumoniae, and 32 H. influenzae) from 35 institutions and archived ocular isolates (760 S. pneumoniae and 356 H. influenzae) from 34 institutions were tested by an independent, central laboratory. Mean minimum inhibitory concentrations that would inhibit growth of 90% of the tested isolates (MIC(90)) were interpreted as susceptible, intermediate, or resistant according to standardized breakpoints for systemic treatment. S. aureus isolates were classified as methicillin susceptible (MSSA) or methicillin resistant (MRSA). RESULTS: MSSA or MRSA susceptibility patterns were virtually identical for the fluoroquinolones, that is, MSSA susceptibility was 79.9% to 81.1% and MRSA susceptibility was 15.2%. Trimethoprim was the only agent tested with high activity against MRSA. All S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; 89.8% were susceptible to ciprofloxacin. H. influenzae isolates were 100% susceptible to all tested agents but trimethoprim. Ocular TRUST 1 data were consistent with the eight-year longitudinal sample of archived ocular isolates. CONCLUSIONS: The fluoroquinolones were consistently active in MSSA, S. pneumoniae, and H. influenzae. After more than a decade of intensive ciprofloxacin and levofloxacin use as systemic therapy, 100% of ocular S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; nonsusceptibility to ciprofloxacin was less than 15%. High-level in vitro MRSA resistance suggests the need to consider alternative therapy to fluoroquinolones when MRSA is a likely pathogen.
Assuntos
Anti-Infecciosos/farmacologia , Infecções Oculares Bacterianas/microbiologia , Haemophilus influenzae/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos , Haemophilus influenzae/isolamento & purificação , Humanos , Resistência a Meticilina , Testes de Sensibilidade Microbiana , Vigilância da População , Estudos Prospectivos , Staphylococcus aureus/isolamento & purificação , Streptococcus pneumoniae/isolamento & purificação , Estados UnidosRESUMO
PURPOSE: To compare the corneal and aqueous penetration and pharmacokinetics of gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions and their effect on corneal reepithelialization after penetrating keratoplasty. METHODS: In this randomized, open-label, parallel-controlled study, corneal and aqueous penetration and the pharmacokinetic parameters of topically applied gatifloxacin 0.3% and moxifloxacin 0.5% (2 preoperative doses of 1 drop given 5 minutes apart) were estimated by using a sparse sampling method. Corneal and aqueous samples were collected 0.25, 0.5, 1, or 2 hours after the final dose. The concentration was determined by a high-performance liquid chromatography method. Stromal Cmax:MBC50 (maximum drug concentration in serum to 50% minimum bactericidal concentration) ratios for selected ocular pathogens were also assessed. Postoperative corneal reepithelialization at days 1, 3, and 7 was evaluated and compared between groups. RESULTS: The calculated pharmacokinetic parameters were higher with moxifloxacin 0.5% than with gatifloxacin 0.3%. The stromal Cmax was 48.5 versus 15.7 microg/g (P = 0.04), and the stromal AUC0-2 (area under the concentration-time curve from 0 to 2 hours) was 30.9 versus 13.6 mug.h/g (P < 0.05). The endothelial Cmax was 76.1 versus 7.3 microg/g (P > 0.05), and the endothelial AUC0-2 was 43.9 versus 9.8 microg.h/g (P < 0.05). The aqueous Cmax was 0.9 versus 0.3 microg/mL (P > 0.05), and the aqueous AUC0-2 was 1.2 versus 0.4 microg.h/mL (P < 0.05). Stromal Cmax:MBC50 ratios were higher in the moxifloxacin 0.5% group for each pathogen tested. The corneal reepithelialization rates were comparable between groups. CONCLUSIONS: Topical preoperative moxifloxacin 0.5% achieved greater corneal and aqueous penetration than did gatifloxacin 0.3%. The clinical significance of this difference is not known. Postoperative use of these agents had similar effects on corneal reepithelialization.
Assuntos
Anti-Infecciosos/farmacocinética , Humor Aquoso/metabolismo , Compostos Aza/farmacocinética , Córnea/metabolismo , Fluoroquinolonas/farmacocinética , Ceratoplastia Penetrante , Soluções Oftálmicas/farmacocinética , Quinolinas/farmacocinética , Administração Tópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos/administração & dosagem , Compostos Aza/administração & dosagem , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Feminino , Fluoroquinolonas/administração & dosagem , Gatifloxacina , Humanos , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Soluções Oftálmicas/administração & dosagem , Quinolinas/administração & dosagem , Distribuição Tecidual , CicatrizaçãoRESUMO
The eye is a common site for complications of human immunodeficiency virus (HIV) infection. Although cytomegalovirus retinitis remains the most prevalent of the blinding ocular disorders that can occur in individuals with the acquired immunodeficiency syndrome (AIDS), several important HIV-associated disorders may involve the anterior segment, ocular surface, and adnexae. Some of these entities, such as Kaposi sarcoma, were well described, but uncommon, before the HIV epidemic. Others, like microsporidial keratoconjunctivitis, have presentations that differ between affected individuals with HIV disease and those from the general population who are immunocompetent. The treatment of many of these diseases is challenging because of host immunodeficiency. Survival after the diagnosis of AIDS has increased among individuals with HIV disease because of more effective antiretroviral therapies and improved prophylaxis against, and treatment of, opportunistic infections. This longer survival may lead to an increased prevalence of anterior segment and external ocular disorders. In addition, the evaluation and management of disorders such as blepharitis and dry eye, which were previously overshadowed by more severe, blinding disorders, may demand increased attention, as the general health of this population improves. Not all individuals infected with HIV receive potent antiretroviral therapy, however, because of socioeconomic or other factors, and others will be intolerant of these drugs or experience drug failure. Ophthalmologists must, therefore, still be aware of the ocular findings that develop in the setting of severe immunosuppression. This article reviews the spectrum of HIV-associated anterior segment and external ocular disorders, with recommendations for their evaluation and management.
Assuntos
Segmento Anterior do Olho/patologia , Oftalmopatias/etiologia , Infecções por HIV/complicações , Antirretrovirais/uso terapêutico , Túnica Conjuntiva/patologia , Córnea/patologia , Oftalmopatias/epidemiologia , Oftalmopatias/prevenção & controle , Pálpebras/patologia , Infecções por HIV/tratamento farmacológico , Humanos , Prevalência , PrognósticoRESUMO
PURPOSE: To evaluate the aqueous humor concentrations and cyclooxygenase (COX) inhibitory activities of nepafenac, amfenac, ketorolac, and bromfenac after topical ocular administration of Nevanac (nepafenac 0.1%), Acular LS (ketorolac 0.4%), or Xibrom (bromfenac 0.09%). SETTING: Five private ophthalmology practices throughout the United States. METHODS: Patients requiring cataract extraction were randomized to 1 of 3 treatment groups: Nevanac, Acular LS, or Xibrom. Patients were administered 1 drop of the test drug 30, 60, 120, 180, or 240 minutes before cataract surgery. At the time of paracentesis, an aqueous humor sample was collected and later analyzed for drug concentration. In addition, COX-1 (homeostatic) and COX-2 (inducible) inhibitory activities of nepafenac, amfenac, ketorolac, and bromfenac were determined via the in vitro measurement of prostaglandin E(2) (PGE(2)) inhibition. RESULTS: Seventy-five patients participated in the study. The prodrug nepafenac had the shortest time to peak concentration and the greatest peak aqueous humor concentration (C(max)). The C(max) of nepafenac was significantly higher than that of the other drugs (P<.05), including the higher-concentration ketorolac (0.4%). The area under the curve (AUC) of nepafenac was significantly higher (P<.05) than the AUCs of amfenac, ketorolac, and bromfenac. The combined AUCs of nepafenac and amfenac were the highest of all drugs tested (P<.05). Ketorolac showed the most potent COX-1 inhibition, whereas amfenac was the most potent COX-2 inhibitor. The PGE(2) aqueous humor levels of each study medication were highly variable; as a result, meaningful interpretation of the data was not possible. CONCLUSION: Nepafenac showed significantly greater ocular bioavailability and amfenac demonstrated greater potency at COX-2 inhibition than ketorolac or bromfenac.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/farmacocinética , Humor Aquoso/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Benzenoacetamidas/farmacocinética , Benzenoacetamidas/farmacologia , Benzofenonas/farmacocinética , Benzofenonas/farmacologia , Disponibilidade Biológica , Bromobenzenos/farmacocinética , Bromobenzenos/farmacologia , Extração de Catarata , Cromatografia Líquida de Alta Pressão , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Dinoprostona/metabolismo , Método Duplo-Cego , Feminino , Humanos , Cetorolaco/farmacocinética , Cetorolaco/farmacologia , Masculino , Pessoa de Meia-Idade , Fenilacetatos/farmacocinética , Fenilacetatos/farmacologiaRESUMO
Two NSAIDs--nepafenac 0.1% and ketorolac tromethamine 0.4%-were compared in terms of their effects on corneal reepithelialization and pain after photorefractive keratectomy (PRK) in a randomized, double-masked, contralateral eye, multicenter study. A total of 40 healthy adult patients who were undergoing sequential bilateral PRK received nepafenac 0.1% and ketorolac 0.4% in contralateral eyes, 1 drop 3 times daily for 3 d after bandage contact lens insertion. Patients were assessed on postoperative days 1, 3, 4, 5, and 7. At each visit, patients provided a general rating of pain. Each patient also assessed the sensation of each eyedrop following instillation (after-drop pain, irritation, burning/stinging, and overall comfort). Starting on day 3, epithelial defect size was assessed. Mean epithelial defect size was similar between treatments at each postoperative visit (P>.05). The average time-to-healing was 4.18 d for nepafenac 0.1% and 4.00 d for ketorolac 0.4% (P=.3134). No statistical difference was observed between nepafenac 0.1% and ketorolac 0.4% in mean postoperative pain scores (P>.05). On day 3, the nepafenac 0.1% group had significantly lower mean sensation scores than did the ketorolac 0.4% group for after-drop pain (P=.0090), irritation (P=.0007), and burning/ stinging (P=.0003). Mean overall comfort score was also significantly better for nepafenac 0.1% on day 3 (7.43 vs 6.41; P<.0001). Nepafenac 0.1% and ketorolac 0.4% provide postoperative pain relief after PRK surgery without associated adverse effects on corneal epithelial healing. Nepafenac 0.1% treatment may offer greater comfort upon instillation in patients who have undergone PRK.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Benzenoacetamidas/uso terapêutico , Epitélio Corneano/efeitos dos fármacos , Cetorolaco/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Fenilacetatos/uso terapêutico , Cicatrização/efeitos dos fármacos , Administração Tópica , Adulto , Método Duplo-Cego , Feminino , Humanos , Lasers de Excimer , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/etiologia , Ceratectomia Fotorrefrativa/efeitos adversosRESUMO
Drugs across many pharmacologic classes induce corneal epithelial changes. Many of these drugs have cationic amphiphilic structures, with a hydrophobic ring and hydrophilic cationic amine side chain that allow them to cross cell membranes. These drugs lead to intracellular phospholipid accumulation, often manifested in the cornea by vortex keratopathy, with no effect on visual acuity and few ocular symptoms. Other drugs, notably antineoplastic agents, produce a fine diffuse corneal haze, sometimes accompanied by decreased vision that can be dose limiting. Still other medications cause crystalline epithelial precipitation that might require debridement for resolution. An understanding of the variety of drugs involved, the multiple mechanisms responsible, and the systemic diseases that produce similar changes can lead to improved management strategies for patients with corneal epithelial deposits. In most cases, drug therapy need not be modified or discontinued, but if visual acuity is affected, close collaboration with the prescribing physician can result in determining an optimized dose that treats systemic disease and minimizes these deposits. Additionally, close monitoring might be required if the drug is also associated with other ocular findings, such as optic neuropathy or retinopathy.
Assuntos
Doenças da Córnea/induzido quimicamente , Epitélio Corneano/efeitos dos fármacos , Doenças da Córnea/patologia , Epitélio Corneano/patologia , HumanosRESUMO
Age-related macular degeneration is the leading cause of blindness in the USA. For the 1.8 million patients in the most advanced stages, there are currently no available treatments to improve vision. A visual prosthetic device that provides one eye with an enlarged retinal image of the central visual field has been developed with the goal of improving central vision in patients with bilateral end-stage macular degeneration. The other eye is left unimplanted to provide peripheral vision. This device is designed for implantation in the posterior chamber of the eye during an outpatient surgical procedure. In US Food and Drug Administration clinical trials, 72% of patients experienced an improvement in their level of visual impairment (profound or severe, to severe or moderate). This was accompanied by a clinically significant improvement in quality of life.
Assuntos
Lentes , Degeneração Macular/cirurgia , Óptica e Fotônica/instrumentação , Transtornos da Visão/reabilitação , Ensaios Clínicos como Assunto , Análise de Falha de Equipamento , Humanos , Degeneração Macular/complicações , Miniaturização , Desenho de Prótese , Qualidade de Vida , Resultado do Tratamento , Transtornos da Visão/etiologia , Transtornos da Visão/cirurgiaAssuntos
Conjuntivite Bacteriana , Conjuntivite Viral , Dexametasona , Humanos , Povidona-Iodo , Estudos ProspectivosRESUMO
BACKGROUND: Several fluorinated carboxyquinolones are used to treat ocular infectious disease. Levofloxacin, in particular, has demonstrated activity against both gram-negative and gram-positive bacteria. OBJECTIVES: An open-label study was undertaken to assess the pharmacokinetics and ocular bioavailability of levofloxacin in human tears, and to determine the tear concentration of levofloxacin in healthy volunteers, following topical administration of a single-dose of 0.5% levofloxacin ophthalmic solution. METHODS: Volunteers received 1 drop of 0.5% levofloxacin in each eye and were assigned sequentially to 1 of 5 groups for tear sampling. Tear samples were collected on Schirmer test strips at 9 predetermined time points ranging from 5 minutes to 24 hours after administration. Six tear samples were collected at each time point (1 eye each from 6 volunteers), except the 24-hour time point, at which 12 samples were collected (both eyes of 6 volunteers). No eye had > 1 tear sample taken during the study. Levofloxacin concentrations were measured using reverse-phase high-performance liquid chromatography. RESULTS: Thirty volunteers were enrolled, with 6 assigned to each of the 5 sampling groups. At 5 minutes after administration of a single topical dose of levofloxacin, the mean tear concentration was 49.19 +/- 26.73 microg/mL. The mean peak concentration of levofloxacin in the tear film, 221.06 +/- 256.68 microg/mL, was reached at 15 minutes after administration. At 4 hours after administration, the mean tear concentration of levofloxacin was 17.04 +/- 15.13 microg/mL. At 6 hours after administration, the mean concentration of levofloxacin was 6.57 +/- 5.26 microg/mL. At 24 hours after administration, levofloxacin concentrations > 2 microg/mL were measured in 2 of 6 (33%) subjects. CONCLUSIONS: Levofloxacin concentrations in the tear fluid after a single topical dose (1 drop) reached high levels quickly and remained above the minimum inhibitory concentration for most suspected ophthalmic pathogens (< or = 2 microg/mL) for at least 6 hours in most healthy volunteers, and for up to 24 hours in some volunteers.
Assuntos
Anti-Infecciosos/farmacocinética , Levofloxacino , Ofloxacino/farmacocinética , Soluções Oftálmicas/farmacocinética , Lágrimas/metabolismo , Administração Tópica , Adolescente , Adulto , Idoso , Anti-Infecciosos/efeitos adversos , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ofloxacino/efeitos adversos , Soluções Oftálmicas/efeitos adversos , Fitas Reagentes , Fatores de TempoRESUMO
PURPOSE: To evaluate the safety and analgesic efficacy of ketorolac tromethamine 0.4% ophthalmic solution in postoperative photorefractive keratectomy (PRK) patients. SETTING: Fifteen clinical sites in the eastern and southern United States. METHODS: This pooled analysis of 2 multicenter, randomized, double-masked, vehicle-controlled, parallel-group studies comprised 313 patients having unilateral PRK. After surgery, patients were treated with 1 drop of ketorolac tromethamine 0.4% ophthalmic solution (Acular(R) LS) (n = 156) or vehicle (n = 157) 4 times daily for up to 4 days. Pain intensity, pain relief, use of escape medication, and severity of ocular symptoms were assessed. Adverse events, epithelial healing, and visual acuity were recorded. RESULTS: There was significantly less pain intensity experienced by patients in the ketorolac group (P<.001). During the first 12 hours post PRK, 50% fewer patients in the ketorolac group than in the vehicle group had severe to intolerable pain (41.6% [64/154] and 84.5% [131/155], respectively). The median time to no pain was 30 hours in the ketorolac group and 54 hours in the vehicle group (P<.001, survival analysis). Ketorolac patients reported significantly greater pain relief than vehicle patients throughout the study (P<.001). Ketorolac patients used significantly less escape medication than vehicle patients for 48 hours post PRK (P< or =.008). Treatment-related adverse events occurred in 2.6% (4/156) of ketorolac patients and 6.4% (10/157) of vehicle patients. CONCLUSION: Ketorolac 0.4% ophthalmic solution is safe and effective in reducing ocular pain when used 4 times daily for up to 4 days post PRK.